PURPOSE: To investigate the rate and source of albumin entry into experimental nonrhegmatogenous detachments. METHODS: Detachments were made in Dutch rabbits by injecting Hanks' balanced salt solution into the subretinal space through a micropipette. Subretinal fluid was withdrawn 0 to 4 hours later through a similar micropipette and analyzed for osmolality and albumin content (by gel electrophoresis). Sodium iodate was injected intravenously in some rabbits to damage the retinal pigment epithelium (RPE). In some rabbits fluorescein isothiocyanate albumin (FITC-albumin) was injected intravitreally or intravenously to measure its entry into the subretinal fluid by fluorophotometry. Results from 4 to 8 eyes were averaged for each data point. RESULTS: The albumin concentration and total amount of albumin in the subretinal fluid increased steadily over 4 hours in retinal detachments initially filled with Hanks' solution. Pretreating rabbits with sodium iodate injection resulted in a 50-fold increase in the rate of albumin entry, although the levels were still low relative to those of serum. Intravitreal FITC-albumin entered the subretinal fluid at a rate independent of sodium iodate damage, but intravenous FITC-albumin only entered the subretinal space after RPE damage. Subretinal fluid osmolality remained within the range of 291 to 294 mOsm/kg, irrespective of sodium iodate damage or differences in the rate of fluid absorption. CONCLUSIONS: These results indicate that albumin can diffuse into the rabbit subretinal space from both vitreous and bloodstream, although entry from serum requires damage to the RPE. Subretinal fluid appears to be transported actively (control eyes) or passively (iodate-damaged eyes) out of the subretinal space, despite albumin entry and without major osmolar shifts.